Phase selective polymer supports for catalysis

ABSTRACT

Phase-selective soluble polymer supports for catalysts are described. The catalysts utilize polystyrene copolymers having enhanced solubility in nonpolar solvents. Other catalysts of the invention utilize polyisobutylene supports. Methods of catalyzing chemical reactions using latent biphasic solvents are also disclosed.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a non-provisional of U.S. Provisional PatentApplication Ser. No. 60/408,586, filed Sept. 6, 2003, which isincorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The invention relates to methods and compositions useful for catalyzingchemical reactions. In particular, phase selective polymer supports forcatalysts and methods of using these supports to facilitate the recoveryof catalysts are disclosed.

BACKGROUND OF THE INVENTION

Polymer supported catalysts are widely used in chemical processes. Muchof the technology that is presently available derives from thesolid-phase peptide synthesis techniques developed by Merrifield. Thesetechniques are based on insoluble cross-linked polystyrene supports.Catalysts supported on Merrifield resins can be recovered from reactionmedia using a solid/liquid separation technique such as filtration.

With the growing interest in environmentally friendly, or “green”chemical processes, there is an emphasis on the ability to reusematerials and to minimize amounts of solvents required for a givenprocess. Filtration is typically a relative solvent-intensive process,because the recovered solid is typically rinsed with additional solvent.Further, some polymer supported catalysts suffer from decreased activityonce they are isolated via filtration. This impacts their potential tobe reused multiple times.

Soluble polymer supported catalysts have been developed. These catalystscan be recovered from the reaction medium either by precipitationfollowed by filtration, by liquid/liquid separation, or byultrafiltration using a filtration membrane. Precipitation/filtrationobviously suffers from the same drawbacks associated with the filtrationof insoluble polymer supported catalysts, described above. Inadequatepartitioning of the catalyst into the desired liquid phase often impairsliquid/liquid separations. For example, liquid/liquid separation isimpractical if the catalyst and the product are both soluble in the samephase. Ultrafiltration of soluble catalysts using membranes has enjoyedsome success, but the recycled catalysts often suffer from some loss ofactivity.

An alternative way of using a soluble catalyst is to use a biphasicsystem wherein the catalyst is preferentially soluble in one phase andthe substrate and/or products are soluble in the other phase. Duringreaction, the biphasic solvent system is vigorously mixed to ensuremaximum contact between the catalyst and substrate. After reaction, themixture is allowed to settle and the product phase is removed, leavingthe catalyst phase available for recycling. The drawback to biphasicsystems is that the presence of multiple phases introduces kineticbarriers to reaction.

The drawbacks associated with biphasic solvent systems can be overcomeby using a solvent system that is monophasic under one set of conditionsand biphasic under a different set of conditions. For example,liquid-liquid biphasic systems that exhibit an increase in phasemiscibility at elevated temperature together with soluble polymer-boundcatalysts that have a strong phase preference at ambient temperature aredescribed in “Palladium-Catalyzed C—C Coupling under ThermomorphicConditions,” by Bergbreiter, et al., J. Am. Chem. Soc., 2000, 122,9058-64 and in “Nonpolar Polymers for Metal Sequestration and Ligand andCatalyst Recovery in Thermomorphic Systems,” by Bergbreiter, et al., J.Am. Chem. Soc., 2001, 123, 11105-06.

There is a need in the art for catalytic methods that allow for theefficient separation of the catalyst from the reaction product and therecycling of the catalyst. It is desirable that such methods operatewith minimal additional solvent to effect the separation of thecatalyst.

SUMMARY OF THE INVENTION

Accordingly, one aspect of the present invention is a method ofcatalyzing a reaction using a solvent system that is monophasic underone set of conditions and biphasic under a different set of conditions.The chemical reaction will occur when the solvent system is monophasic.At the end of the reaction, the solvent system is switched to thebiphasic state. The reaction product is preferentially soluble in one ofthe phases and the polymer-supported catalyst is preferentially solublein the other phase.

According to one embodiment, the product-containing phase can be removedand replaced by a fresh polar phase and more reactants, allowing thecatalyst to be recycled.

A further aspect of the present invention is a catalytically activecomposition comprising a polystyrene copolymer, the polystyrenecopolymer comprising styrene monomers substituted with one or morecatalytically active functional groups and pendant styrene groupssubstituted with one or more functional groups that increase thesolubility of the polystyrene copolymer in a non-polar solvent.

A still further aspect of the present invention is a catalyticallyactive composition comprising a catalytically active functional groupbound to polyisobutylene.

DETAILED DESCRIPTION OF THE INVENTION

One aspect of the present invention is a method of catalyzing a chemicalreaction using a latent biphasic liquid solvent system. As used herein,the term latent biphasic system refers to a mixture of solvents, whereinthe mixture is monophasic under one set of conditions and biphasic undera different set of conditions. The liquid solvent components aremiscible in the monophasic state. The biphasic state comprises a morepolar phase and a less polar phase, with the two phases being layered,one on top of the other. The latent biphasic system facilitatesseparating the catalyst from the reaction products because the system isdesigned so that the catalyst is preferentially soluble in one phase ofthe biphasic mixture and the products are preferentially soluble in theother phase. Typically, the chemical reaction will occur when thesolvent system is in the monophasic state. Because the reaction mediumis in the monophasic state, the reaction is not impeded by phasetransfer phenomena or other kinetic barriers associated with multiplephase reactions. Following the reaction, the solvent mixture is switchedto the biphasic state to facilitate separating the products from thecatalyst.

According to one embodiment of the invention, the phase containing thecatalyst is recycled and used for multiple reaction cycles. For example,if the catalyst is preferentially soluble in the less polar of thephases of the biphasic mixture and the reaction products arepreferentially soluble in the more polar of the phases, then a recyclingreaction protocol is defined by the following sequence:

-   -   1) A substrate and/or reactants are present in the latent        biphasic system, along with the catalyst. The reaction proceeds        while the latent biphasic system is in the monophasic state.    -   2) The latent biphasic system is perturbed to switch the system        to the biphasic state comprising a more polar phase containing        the reaction products and a less polar phase containing the        catalyst.    -   3) The more polar phase containing the reaction products is        separated from the less polar phase containing the catalyst.    -   4) Additional substrate and/or reactants, along with the more        polar solvent components are added to the catalyst-containing        phase. The solvent system is switched to the monophasic state        and the reaction proceeds. The cycle is repeated.

Mixtures of solvents have a spectrum of phase behavior. For example,ethanol and water are miscible in all proportions, as are ethanol andheptane. However, mixtures containing all three of these components varyin miscibility depending on several factors, including the proportionsof each of the components, temperature, and the presence or absence ofsolute. For example, a 10.0:9.5:0.5 (vol:vol:vol) mixture of heptane,ethanol, and water is monophasic at 25° C., but a mixture of the samecomponents with a ratio of 10.0:9.5:1.0 is biphasic at the sametemperature. Therefore, heptane, ethanol, and water can be used ascomponents for a latent biphasic system. The monophasic state is amixture having the composition of about 10.0:9.5:0.5 (vol:vol:vol).Adding an additional 0.5 volumetric equivalents of water perturbs thesystem and induces phase separation.

Countless latent biphasic systems are possible. For example, a misciblemixture of 10 mL each of toluene and 95% ethanol/water becomes biphasicon addition of 0.5 mL of water. Likewise, a mixture oftert-butylmethylether, ethanol, and water having a volumetric ratio of10.0:6.0:4.0 is miscible. Adding an additional 2.5 volumetricequivalents of water switches the mixture to a biphasic state. It iswithin the ability of one of skill in the art to derive other latentbiphasic solvent systems without undue experimentation.

Phase separations in many latent biphasic solvents can be initiated byadding a salt to the solvent. If a salt is a side product of thecatalytic reaction of interest, then the production of the salt in situcan induce phase separation.

Other examples of latent biphasic systems include mixtures of solventsthat are homogeneous within one temperature range and biphasic within adifferent temperature range. Herein, these systems are referred to asthermomorphic latent biphasic systems. For example, a mixture of equalvolumes of heptane and 90% ethanol/water are completely miscible at 70°C. Cooling the mixture to 25° C. produces a biphasic mixture with a lessdense non-polar phase containing mostly heptane and a denser polar phaseof mostly ethanol and water. Likewise, N,N-dimethylacetamide and heptaneare immiscible at 25° C. but are miscible in all proportions above 65°C.

In a separation scheme utilizing latent biphasic mixtures for catalyticreactions, it is desirable that the catalyst selectively partition intoone of the two phases of the biphasic state. For example, if thecatalyst is preferentially soluble in the non-polar phase, the ratio ofthe amount of catalyst that ends up in the non-polar phase compared tothe amount that ends up in the polar phase is ideally greater than 10:1,more ideally greater than 100:1 and even more ideally greater than200:1. If the catalyst-containing phase is to be recycled throughmultiple reaction cycles, it is desirable that the ratio be at leastabout 200:1.

One aspect of the present invention is a catalytically activecomposition comprising a polystyrene copolymer. The copolymer comprisesstyrene monomers substituted with one or more catalytically activefunctional groups and styrene monomers substituted with one or morelipophilic groups. The copolymers of the present invention can comprisetwo or more types of monomers. For example, the copolymer can compriseone type of monomer that is catalytically active and one type of monomerthat is substituted with a lipophilic group. Alternatively, thecopolymer. can comprise one type of monomer that is catalytically activeand more than one type of monomer that is substituted with a lipophilicgroup. According to another embodiment, the copolymer can comprise onetype of monomer that is catalytically, active, one or more types ofmonomers substituted with lipophilic groups, and also unsubstitutedpolystyrene.

As used herein, lipophilic group refers to any functional group thatincrease the solubility of the polystyrene copolymer in a non-polarsolvent. An example class of lipophilic groups, as the term is usedherein, is alkyl groups. Alkyl groups that are particularly suitable forimparting solubility include alkyl groups having four to about eighteencarbons. Alkyl groups can be branched, cyclic, or straight chained. Aparticularly suitable alkyl-substituted styrene is tert-butylstyrene.Examples of suitable alkyl groups include n-butyl, t-butyl, pentyl,hexyl, heptyl, octyl, decyl, dodecyl, tetradecyl, hexadecyl, andoctadecyl groups. Other lipophilic groups include aliphatic groups thatcontain ether linkages, multiple bonds, hydroxy groups, esters, amides,triorganosilyl ethers, and the like. Aliphatic groups can be attached tothe styrene monomer through a carbon-carbon bond directly to the styreneor it can be attached via another functional group such as an ether,ester, or amide linkage. Examples include fatty acid derivatives ofstyrene, having the fatty acid connected to the styrene aromatic ringvia an ester linkage. Such fatty acids can be saturated or unsaturated.Examples include lauric, mysristic, palmitic, stearic, arachidic, oleic,linoleic, linolenic, and arachidonic derivatives of the styrene monomer.Styrene monomers can be substituted at either the ortho-, meta-, orpara-, position of the aromatic ring or they can be multiplysubstituted.

Examples of styrene monomers substituted with one or more catalyticallyactive functional groups can include styrene monomers substituted withany species that catalyzes a particular reaction. The catalytic speciescan be an organic group. Organic catalysts can be bound directly to thestyrene monomer or they can be connected to the styrene monomer via alinking moiety.

A styrene copolymer wherein some of the styrene monomers are substitutedwith a triorganophosphine can be used to catalyze a Michael additionreaction. Examples of triorganophsphines include trialkylphosphines andtriarylphophines. An example of such a copolymer, which contains atriarylphosphine, is shown in Formula 1.

An illustrative embodiment utilizing a supported catalyst of Formula Iis a Michael reaction between 2-nitropropane and methylacrylate(Reaction 1). The catalyst is dissolved in heptane. An equal volume ofan ethanol solution containing the nitropropane and methylacrylate isadded and the monophasic mixture is stirred for about 24 hours at about25° C. About 10%, by volume, of water is then added to induce phaseseparation. The Michael reaction product is soluble in the polar phaseand the catalyst is soluble in the non-polar phase. Adding a freshethanol solution of 2-nitropropane and methylacrylate to the non-polargenerates a monphasic system and begins a subsequent cycle of thecatalytic reaction.

A polystyrene copolymer wherein some of the styrene monomers aresubstituted with a nucleophilic moiety can catalyze the acylation ofphenols. Examples of such copolymers comprise styrene monomerssubstituted with heterocyclic nucleophilic groups such as imidazoles,thiazoles, substituted pyridines, and (4-pyridylpiperazine). An exampleof such a copolymer is shown in Formula II.

Metal complexes are another example of catalytic species. Metalcomplexes can be incorporated onto styrene copolymers wherein some ofthe styrene monomers are substituted with appropriate ligand species toform a complex with the metal. For example, a styrene copolymer whereinsome of the styrene monomers are substituted with3,5-bis(phenylthiomethyl)phenyl palladium chloride can be used tocatalyze C—C coupling reactions.

Polystyrene, wherein some of the styrene monomers are substituted withadiorganophosphine can support palladium and be used for palladiumcatalyzed C—C bond formation via Suzuki or Heck coupling. An example ofsuch a diorganophosphine is diadamantylphosphine. In a typical example,about 0.1 to about 2 mol% of a palladium(0) source is added to an excessof the poly(tert-butylstyrene)-supported phosphine ligand in heptane.Addition of a substrate iodoarene and an acceptor (e.g. a arylboronicacid for Suzuki chemistry or a α,β-unsaturated carbonyl compound forHeck chemistry) in a second solvent (e.g. N,N-dimethylacetamide,N,N-dimethylformamide or ethanol) followed by heating leads to C—C bondformation in a Suzuki or Heck coupling. Cooling (or addition of water orsalt) produces a biphasic mixture, allowing the nonpolarcatalyst-containing phase to be separated from the polarproduct-containing phase and reused in subsequent reaction cycles.

Copolymers of the present invention can further comprise styrenemonomers substituted with one or more functional groups that aid in thequantification of the amount of the copolymer that resides in aparticular phase. Examples of such functional groups are dyes,fluorescent probes, and other functional groups containing chromophores.Absorbance, fluorescence spectroscopy, or visible inspection can be usedto determine the partitioning of such copolymers in a particular phase.

Copolymers of the present invention can be prepared by copolymerizingthe component styrene monomers, that is, copolymerizing thecatalytically active substituted styrene monomers with the substitutedstyrene monomer having enhanced solubility. Many techniques forcopolymerizing styrene are known in the art. An example of aparticularly suitable technique is polymerization in toluene, usingbenzoyl peroxide as an initiator. The two monomers are added to asolution of toluene, along with benzoyl peroxide, and the mixture isheated. The reaction can be heated for a length of time of a few hoursto a few days. It is typically desirable that the reaction be carriedout in an inert atmosphere, for example nitrogen or helium. The ratio ofthe two monomers can vary, depending on the desired ratio of themonomers in the resulting copolymer. In general, the ratio of themonomers in the resulting copolymer will be approximately the same asthe ratio of the monomers in the polymerization reaction. The amount ofbenzoyl peroxide initiator is typically 0.5 mol % to about 10 mol %,based on the monomers. Benzoyl peroxide-initiated polymerization is wellknown in the art and it is within the ability of one of skill in the artto optimize a copolymerization based on one's particular targetcopolymer.

A copolymer of Formula II can be synthesized by addingtert-butylstyrene, 1-(4-vinylbenzyl)-4-pyridylpiperazine, and benzoylperoxide to toluene at a molar ratio of about n:m:0.01n. The toluenemixture is heated at about 70° C. for about 24 hours, preferably underan inert atmosphere such as nitrogen. Adding a polar liquid, such asmethanol, precipitates the resulting copolymer.

An alternative method of producing copolymers of the present inventionis to copolymerize monomers that are substituted with a reactive group,which can subsequently be transformed into the desired substituent byperforming a reaction on the copolymer. For example, a copolymeraccording to Formula I can be prepared by copolymerizingtert-butylstyrene with a phosphine oxide substituted styrene derivativeto yield a copolymer containing tert-butylstyrene monomers and phosphineoxide substituted monomers. This copolymer is then reduced by reactionwith trichlorosilane and triethylamine to produce the catalyticallyactive triarylphosphine-substituted copolymer.

Another example of a copolymer containing a reactive precursor group isa copolymer of tert-butylstyrene as the solubility-enhanced monomer andchloromethylstyrene as the reactive precursor monomer. Such a copolymercan be reacted with a catalytically active species containing analkoxide to attach the catalytically active species via an etherlinkage. Alternatively, the copolymer can be reacted with acatalytically active species containing a carboxylic group to attach thecatalytically species via an ester linkage. It should be apparent to oneof skill in the art that these methods can also be used to attach aprobe species, such as a dye molecule, to the copolymer.

Poly(4-tert-butylstyrene-c-vinylbenzyl chloride) can also be used as astarting material for a poly(tert-butylstyrene) supporteddiorganophosphine complex wherein the phosphorous is bonded directly tothe styrene aromatic ring. Such poly(tert-butylstyrene) supporteddiorganophosphine copolymers are described above as supports forpalladium catalysts. In a typical example, a diorganophosphine-boranecomplex is deprotonated and reacted withpoly(4-tert-butylstyrene-c-vinylbenzyl chloride). Removal of the boraneyields the poly(tert-butylstyrene)-supported diorgaonophosphine.

A further aspect of the present invention is a catalytically activecomposition comprising a polyisobutylene polymer or oligo-isobutylenethat contains a catalytically active species. The catalytically activespecies can be any of the types of catalysts discussed above. Suchmodified polyisobutylenes are useful for catalytic reactions in latentbiphasic systems because the polyisobutylene is typically preferentiallysoluble in the less polar phase and can therefore be separated fromreaction products that are preferentially soluble in the more polarphase.

Modified polyisobutylenes and oligo-isobutylenes of the presentinvention can be produced from polyisobutylenes and oligo-isobutylenesthat have reactive terminal groups. One example of sucholigo-isobutylenes is shown in Formula III.

Oligo-isobutylenes of Forumla III provides a synthetic route tocatalytically active species via well known chemical transformations.For example, the terminal alkene can be brominated by reaction withhydrogen bromide, and a catalytically active species containing ahydroxy group can be attached to the resulting bromine terminal polymervia a Williamson ether synthesis.

Oligo-isobutylenes of Formula III can be used as a starting material fora supported triorganophosphine ligand, which can in turn be used as asupport for a palladium catalyst. For example the terminal vinyl groupcan be oxidized to a hydroxy group via an oxidation such ashydroboration-oxidation. The resulting oligomer can then converted intoa —CH₂OSO₂CH₃ terminated oligomer using CH₃SO₂Cl and triethylamine. Thismesylate can then be either converted into a —CH₂Br-terminated oligomerusing NaBr or into a —CH₂CO₂H-terminated oligomer using a malonic estersynthesis prior to formation of a phosphine ligand or catalyst. In thecase of —CH₂CO₂H, a phosphine can be attached to the oligomer by amideformation using EtO₂CCl and N-methylmorpholine to activate the —CO₂H,followed by addition of a diorganophosphine-organoamine such asdiphenylphosphine-propylamine (DPPA). In the case of the —CH₂Brterminated oligomer, a phosphine can be attached by C—P bond formationusing lithiated diorganophosphine-borane. The resultingtriorganophosphine-substituted oligomer can be mixed with a palladium(0)source such as Pd₂(bda)₃, to yield a supported palladium catalyst.

EXAMPLES Example 1

Unless otherwise noted, the general preparatory procedures described inthis example were used for all of the examples. 4-tert-Butylstyrene wasdistilled before use. Benzoyl peroxide was recrystallized fromCHCl₃/methanol. Toluene was distilled under nitrogen. Gaschromatographic analyses was performed on a Shimadzu instrument equippedwith a 15-m SPB (poly(5%-diphenyl-95% dimethylsiloxane) normal phasefused-silica capillary column (0.53 ID). ¹H NMR spectra were recorded onVarian VXR-300 or Unity p300 spectrometers at 300 MHz. Chemical shiftswere reported in ppm with CHCl3 (7.27 ppm) as the internal standard. ¹³CNMR spectra were recorded at 75 MHz with CDCl₃ (77.23 ppm) as theinternal reference. Chemical shifts of ³¹P NMR spectra were reported inppm with H₃PO₄ (0 ppm) as the internal standard. Gel permeationchromatography was performed using a Ranin SD-200 HPLC system equippedwith Dynamax UV-C detector (at 254 nm). A TOSOH BIOSEP column (μm) wasused. THF was used as the eluent.

Dye-labeled tert-butylstyrene copolymer. A copolymer containingtert-butylstyrene monomers and dye-labeled styrene monomers was producedto probe the phase selectivity (poly)tert-butylstyrene. METHYL RED wasthe dye. Dye-substituted styrene monomer was prepared by dissolving 1.4mL of 4-vinylbenzylchloride and 1.346 g of METHYL RED in 5 mL ofdistilled dimethylformamide (DMF) in the presence of 1.05 mL oftriethylamine. The solution was stirred for 24 h and then poured into 50mL of water. The resulting solid precipitate was isolated by filtrationand purified by column chromatography using 4:1 (vol:vol) hexane:ethylacetate as the eluent. The product was isolated in 94% yield. ¹H NMR(CDCl₃): δ 8.2 (d, 8.8 Hz, 2H), 7.9 (dd, J =8.8, 9.3 Hz, 4H), 7.4 (s,4H), 6.8 (d, 9.3 Hz, 2H), 6.7 (dd, J =11.0,17.6 Hz, IH), 5.8 (d, 17.6Hz, IH), 5.4 (s, 2H), 5.3 (d, 11.0 Hz, 1H), 3.1 (s, 6H). ¹³C NMR: δ166.4, 156.3, 153.1, 143.9, 137.8, 136.6, 135.7, 130.9, 130.2, 128.7,126.6, 125.7, 122.2, 114.6, 111.7, 66.8, 40.5. MS (ESI): 386 (M+Ht,calcd 386.454, found 386.185.

Dye-labeled poly(4-tert-butylstyrene)was prepared by dissolving 1 mL of4-tert-butylstyrene, 10 mg of dye-substituted styrene, and 12 mg ofbenzoyl peroxide in 10 mL of toluene under nitrogen. The solution washeated at 70° C. for 24 hours, cooled to room temperature, and addeddropwise to 50 mL of methanol to precipitate the polymer. ¹H NMR: δ7.2-6.1 (br, m, 4H), 2.0-1.4 (br, m, 3H), 1.2 (bs, 9H). UW: 427 inheptane.

The copolymer was characterized by GPC and was found to have an M_(n) of23,000 Da and an M_(w) of 48,000 Da. It was readily soluble in heptane.The dye-labeled copolymer was phase selectively soluble in heptane whenanother polar phase was present. Specifically, when the copolymer wasfirst dissolved in heptane and then mixed with an equal volume of eitherDMF or 90% aqueous ethanol, a biphasic mixture formed with a hellowheptane phase. Heating either of the biphasic solutions to 70° C.produced a monophasic mixture. Cooling these thermomorphic mixtures backto room temperature reformed the biphasic solution. UV-visiblespectroscopic analysis of the non-polar and polar phases showed nodetectable dye in the non-polar phase.

The dye-labeled copolymer was dissolved in a miscible mixture (1:1,vol:vol) of heptane and ethanol. Addition of 10 vol. % of water produceda biphasic mixture. The dye-labeled copolymer was exclusively soluble inthe less polar heptane-rich phase of the biphasic mixture.

Example 2

Poly(4-tert-butylstyrene)-co-poly(4-vinlybenzylchloride). A mixture of18.3 mL of 4-tert-butylstyrene, 1.4 mL of 4-vinylbenzyl chloride and 240mg of benzoyl peroxide were dissolved in 100 mL of toluene undernitrogen, and the solution was heated at 70° C. for 24 hours. Aftercooling to room temperature, the solution was added dropwise to 500 mLof methanol to precipitate the product polymer. The product polymer wascharacterized by ¹H NMR spectroscopy (CDCl₃) δ 7.2-6.1 (br, m, 44H),4.6-4.4 (br, s, 2H), 2.0-1.4 (br, m, 33H), 1.2 (br, s, 90H).

Example 3

Dye-labeled poly(4-tert-butylstyrene) supported phosphine catalyst forMichael addition. Phosphine oxide substituted styrene was prepared bydissolving 4.9 g of 4-diphenylphosphinobenzoic acid and 6 mL ofdicyclohexylamine 20 mL of DMF and heating the solution to 70° C. for 20minutes. At that point, 2.25 mL of 4-vinylbenzyl chloride was added,followed by a small amount of NaI. The mixture so formed was heatedovernight. After filtration to remove the solid that formed, the DMFsolution of the product was poured into water and extracted withdichloromethane. A crude product was obtained after removal of theCH₂Cl₂ under reduced pressure. This crude product was passed throughsilica gel, using 1: 1 hexanes:ethyl acetate as the eluent. Removal ofthe solvent yielded the product in 63% yield. ¹H NMR: δ 8.2 (d, 5.9 Hz,2H), 7.8-7.4 (m, 16H), 6.7 (dd, J=10.7, 17.5 Hz, IH), 5.8 (d, 17.5 Hz,IH), 5.4 (s, 2H), 5.2 (d, 10.7 Hz, IH). ¹³C NMR: δ 165.8, 136.5, 136.3,133.4, 132.5, 132.4, 132.3, 132.2, 131.6, 129.8, 129.7, 128.9, 128.8,126.7, 114.7,67.1. ³¹P NMR (CDCl₃): 029.0. MS (ESI): 439 (M+H)⁺, calcd439.434, found 439.143.

Dye-labeled poly(4-tert-butylstyrene) supported phosphine oxide wasprepared by mixing of 5 mL of 4-iert-butylstyrene, 600 mg of thephoshpine oxide substituted styrene, 5.3 mg of dye substituted styreneand 63 mg of benzoyl peroxide in 50 mL of toluene under nitrogen, thenheating at 70° C. for 24 hours. The solution was then cooled to roomtemperature, and added dropwise into 300 mL of methanol. Afterfiltration, the solid was dried under vacuum. ¹H NMR: δ 8.1-7.4 (m,10H), 7.1-6.0 (m, 88H), 4.8 (bs, 2H), 2.2-1.4 (m, 63H), 1.2 (bs, 180H).³¹P NMR (CDCl₃): δ29.1. UV: 430 nm in heptane.

The active catalyst was prepared by preparing a toluene solution (10 mL)containing 1 g of the polymer-supported phosphine oxide under nitrogen.Then, 0.14 mL of trichlorosilane and 0.21 mL of triethylamine were addedand the solution was heated at reflux overnight. The product solutionwas then cooled down to room temperature and poured into 100 mL ofmethanol. After filtration, the solid was dried under vacuum. ¹H NMR: δ8.1-7.4 (m, 10H), 7.2-6.0 (m, 88H), 5.0 (bs, 2H), 2.4-1.5 (m, 63H), 1.2(bs, 180H). ¹³C NMR: δ 165.8, 138.3, 137.9, 137.5, 136.4, 135.2, 132.5,132.4, 132.3, 132.2, 129.7, 128.9, 128.8, 126.7, 114.7, 67.2. ³¹P NMR(CDCl₃): δ −4.7. UV: 430 nm in heptane.

Michael addition was performed in a latent biphasic solution. A heptanesolution of 365 mg of the polymer-supported catalyst was prepared using10 mL of heptane. Separately, 0.18 mL of 2-nitropropane and 0.09 mL ofmethylacrylate were dissolved in 10 mL of ethanol. The two solutionswere mixed and stirred for 24 hours. Water (1.5 mL) was added to thehomogeneous mixture to induce phase separation. UV-visible spectroscopyshowed that all of the copolymer was in the nonpolar phase. The ethanolphase was concentrated under vacuum to isolate the product, and theheptane phase was mixed with fresh substrates for the next cycle. Theisolated yields of Michael addition product through the first fivecycles were 31.5, 56.7, 69.0, 72.5, and 71.1%, respectively.

The initially low yield increases with increasing cylcle number becausethe product has some solubility in heptane. The product in the firstcycle only represents the product that partitions into the aqueousethanol phase. As the cycle number increases, the heptane phaseeventually gets saturated with the product and the isolated yield fromthe ethanol phase increases.

Example 4

Dye-labeled poly(4-tert-butylstyrene)-supported pyridylpiperazinecatalyst for the acylation of phenols. 4-Vinylbenzylchloride was passedthrough neutral alumina to remove any inhibitors.1-(4-Vinylbenzyl)-4-pyridylpiperazine was prepared by dissolving 4.32 mLof 4-vinylbenzylchloride and 10 g of N-(4-pyridyl)piperazine in 100 mLof methanol. The solution was allowed to reflux overnight. After coolingto room temperature, 20 mL of 6 N HCl was added and the solution wasextracted three times with ether. The ether extracts were discarded and20 g of NaOH in 20 mL of water was added dropwise to the aqueoussolution. The resulting precipitate was recovered by filtration andpurified by colum chromatography using 5% triethylamine in ethyl acetateas the eluent. Removal of the solvent under reduced pressure producedthe product in 72.1% yield. ¹H NMR: δ 8.2 (d, 6.6 Hz, 2H), 7.3 (dd,J=6.4, 6.6 Hz, 4H), 6.7 (dd, J=10.7, 17.6 Hz, 1H), 6.6 (d, 6.4 Hz, 2H),5.7 (d, 17.6 Hz, 1H), 5.2 (d, 10.7 Hz, 1H), 3.5 (s, 1H), 3.3 (t, 5.2 Hz,4H), 2.5 (t, 5.1 Hz, 4H). ¹³C NMR: δ 155.2, 150.4, 137.6, 136.9, 136.7,130.0, 126.4, 113.9, 108.5, 62.9, 52.7, 46.1.

Dye-labeled poly(4-tert-butylstyrene)-supported pyridylpiperazinecatalyst was prepared by dissolving 6.6 mL of 4-tert-butylstyrene, 1 gof 1-(4-Vinylbenzyl)-4-pyridylpiperazine, 50 mg of dye-substitutedstyrene, and 87 mg of benzoylperoxide in 50 mL of toluene undernitrogen. The mixture was heated at 70° C. for 24 hours. After coolingto room temperature, the solution was added dropwise to 300 mL ofmethanol to precipitate the product polymer. ¹H NMR: δ 8.2 (bs, 2H),7.2-6.1 (br, m, 86H), 3.2 (bs, 4H), 2.5 (bs, 4H), 2.0-1.4 (br, m, 63H),1.2 (bs, 180H). UV: 425 nm in heptane.

The copolymer was used to catalyze the formation of a t-butlydicarbonate(t-Boc) derivative of 2,6-dimethylphenol by dissolving 88 mg of thepolymer in 4 mL of heptane. Separately, 305 mg of 2,6-dimethylphenol and57 mg of Boc₂O were dissolved in 4 mL of ethanol. The two solutions weremixed and the resulting homogeneous mixture was stirred for 1 hour.Water (0.6 mL) was added to induce phase separation. The catalystquantitatively partitioned into the heptane-rich phase. The ethanolphase was concentrated under vacuum to isolate the product. Freshsubstrates were mixed with the catalyst-containing heptane phase for thenext cycle. The yields of the t-Boc derivative for the first five cycleswere 34.3, 60.9, 82.2, 94.6, and 99%. The subsequent yields over 20cycles were essentially quantitative.

Example 5

Poly(4-tert-butylstyrene) supported diadamantylphosphine as a Pd ligandfor Pd(0) Catalysis. A poly(4-tert-butylstyrene) supported diadamantylphosphine-borane complex was produced by reactingdiadamantylphosphine-borane with poly(4-tert-butylstyrene-c-vinylbenzylchloride). Diadamantylphosphine-borane (0.45 g, 1.42 mmol, 2.5 eq) wasintroduced to a 100-mL flame-dried round bottom flask equipped with astir bar and septa, and kept under a positive pressure of N₂. The solidwas dissolved in 30 mL of freshly distilled THF and cooled to −78° C.Deprotonation of the phosphine borane complex was accomplished by theaddition of 0.89 mL (1.42 mmol, 2.5 eq) of a 1.6 M n-BuLi solution inhexanes and stirring at −78° C. for 2 hours before warming the mixtureto room temperature and stirring for an additional 12 hours. Thereaction temperature was brought back to 78° C. and 1.0 g (0.57 mmol, 1eq) of dry 10:1 poly(4-tert-butylstyrene-c-vinylbe chloride) was placedin a flame-dried 25 mL flask and dissolved in 10 mL of freshly distilledTHF. The polymeric solution was then transferred by forced siphon intothe reaction flask, which was kept at −78° C. for another 2 h beforewarming to room temperature and stirring for 12 h. The THF was removedunder reduced pressure and the polymeric product was dissolved into 100mL of hexanes. The hexanes solution was washed with 50 mL (×10) ofhexanes saturated DMF. The hexane was removed under reduced pressure,the polymer dissolved into 100 mL of diethyl ether and washed with 20 mL(×5) of H₂O. The ether layer was dried over Na₂SO₄, the ether removedunder reduced pressure, and the product dried under vacuum for 12 hoursto give poly(4-tert-butylstyrene) supported diadamantyl phosphine-boranecomplex in 89% yield. ¹ H NMR: (CDCl₃) δ 6.1-7.2 (br, m, 45H), δ 2.9-3.1(br, s, 2H), δ 1.0-2.2 (br, m, 156H). ³¹P NMR: (benzene) δ 36.42 (br,s).

Poly(4-tert-butylstyrene) supported diadamantylphosphine-borane complex(1.03 g, 0.51 mmol) was transferred to a 40 mL reaction tube containing15 mL of morpholine and sealed with a septa. The reaction mixture wasdegassed and the sealed system was heated to 110° C. for 36 hours. Aftercooling to 40° C., the morpholine was removed under reduced pressure. 15mL of degassed hexanes was then transferred to the reaction tube viaforced siphon and the polymer completely dissolved prior to the additionof 15 mL degassed 90% ethanol. The mixture was stirred to ensureextraction of the morpholine-borane complex into the 90% ethanol phaseand the phase subsequently removed by forced siphon. The 90% ethanolextraction was repeated and the hexane layer was then transferred byforced siphon to a degassed flask containing Na₂SO₄ and allowed to dry.The dried hexane phase was then transferred by forced siphon into anempty, preweighed, degassed flask and the hexanes removed by reducedpressure. The product was then dried in vacuo for 12 h to givepoly(4-tert-butylstyrene) supported diadamantyl phosphine in 90% yieldand 9% oxidation. ¹H NMR: (benzene) δ 6.4-7.5 (br, m, 51H), δ 2.7-3.0(br, s, 2H), δ 1.1-2.6 (br, m, 173). ³¹P NMR: (benzene) δ 46.15 (br, s,9P), δ 29.30 (br, s, 91P).

The poly(tert-butylstyrene)-bound —CH₂PAd₂]₂Pd(0) catalyst was preparedusing Pd₂(bda)₃ as the Pd(0) source. The catalyst was used to catalyzethe conversion of iodobenzene and tert-butylacrylate totert-butylcinnamate in a mixture of N,N-dimethylacetamide and heptane at120° C. over 12 h using triethylamine as a stoichiometric base. Coolingthis mixture produced a biphasic solution (due to the presence ofbyproduct triethylammonium iodide salt). The catalyst-containing heptanerich phase was isolated and recycled by adding it to a fresh solution ofsubstrates.

Example 6

Polyisobutylene supported Palladium Catalyst. A vinyl terminatedpolyisobutylene oligomer (M_(w) of 1000 or 2000) (e.g. 50 g (50 mmol) ofPIB₁₀₀₀) was converted into 52 g of —CH₂OH-terminated oligomer usinghydroboration oxidation with BH₃SMe and basic 30% aqueous H₂O₂. Thisoligomer was then converted into 54.5 g of a —CH₂OSO₂CH₃ terminatedoligomer using CH₃SO₂Cl and Et₃N in CH₂Cl₂. This polyisobutyl (PIB)mesylate was then converted into a —CH₂CO₂H-terminated oligomer using amalonic ester synthesis. A phosphine was attached to the oligomer byamide formation using EtO₂CCl and N-methylmorpholine to activate the—CO₂H group prior to addition of diphenylphos-phinepropylamine (DPPA).The product alkyldiarylphosphine was prepared on a 2 g scale and wascharacterized by NMR spectrosocopy: ¹H NMR (300MHz, CDCl₃, δ):0.81-1.65(m), 2.00-2.12(m), 3.28-3.35(m), 7.29-7.40(m); ³¹P NMR (CDCl₃,δ):−15.83.

An alternative route to the alkyldiarylphosphine was to convert thepolyisobutyl mesylate (PIB—CH₂OSO₂CH₃) into a —CH₂Br-terminated oligomerusing NaBr. A phosphine was attached to the PIB—CH₂Br oligomer by C—Pbond formation using lithiated dicyclopentyl phosphine-borane in THF.The 1.8 g of product had ¹H NMR (300MHz, CDCl₃, δ): 0.81-1.39(m),1.52-1.68(m), 1.82-1.87(m), 1.94-2.05(m) and ³¹P NMR (CDCl₃, δ): 25.98.The same procedure also afforded a diadamantylphosphine-boraneterminated PIB oligomer using lithiated diadamantylphosphine-borane asthe nucleophile. Removal of the BH₃-protecting group was effected byaddition of a secondary amine. The free phosphine so formed wascharacterized by ³¹P NMR spectroscopy (e.g. the dicyclopentylphosphineterminated oligomer had a ³¹P NMR. peak at −11.06δ (C₆D₆).

Pd(0) PIB phosphine ligated catalysts were prepared byPIB-triorganophosphine with a Pd(0) source. A solution of 9.15 mg ofPd₂(bda)₃ (0.01 mmol) in 10 mL of THF was added to a solution ofPIB—CH₂CONH(CH₂)₃PPh₂(6)(0.08 mmol) in 2 mL of heptane. The Pd(0)catalyst so formed was then used in catalytic reactions. For example, 10mL of this solution were added to 10 mL of a 90% ethanol solutioncontaining iodobenzene, phenylacetylene, triethylamine and CuI. Heatingthe resulting biphasic system to 75° C. led to miscibilization andconversion of the haloarene to an arylalkyne. After reaction, coolinginduced phase separation. The product diphenylacetylene in this examplewas isolated from the lower phase. The upper phase was recycled using afresh 90% ethanol solution of the other reactants.

1. A catalytically active composition comprising a polystyrenecopolymer, the polystyrene copolymer comprising a first styrene monomerand a second styrene monomer, wherein the first styrene monomer issubstituted with one or more catalytically active functional groups andthe second styrene monomer is substituted with one or more lipophilicgroups.
 2. The composition of claim 1, wherein the first styrene monomeris substituted with a triorganophosphine.
 3. The composition of claim 1,wherein the first styrene monomer is substituted with atriarylphosphine.
 4. The composition of claim 1, wherein the firststyrene monomer is substituted with a nucleophilic organic catalyst. 5.The composition of claim 1, wherein the first styrene monomer issubstituted with a catalyst selected from the group consisting ofimidazoles, thiazoles, pyridines, and (4-pyridylpiperazine).
 6. Thecomposition of claim 1, wherein the first styrene monomer is substitutedwith 4-pyridylpiperazine.
 7. The composition of claim 1, wherein thefirst styrene monomer is substituted with a metal complex.
 8. Thecomposition of claim 1, wherein the first styrene monomer is substitutedwith a metal complex selected from the group consisting of3,5-bis(phenylthiomethyl)phenyl palladium chloride anddiadamantylphosphine palladium.
 9. The composition of claim 1, whereinthe second styrene monomer is substituted with a functional groupselected from the group consisting of hydrocarbons, hydrocarbonssubstituted with one or more ester groups, hydrocarbons containing oneor more ether groups, and hydrocarbons containing one or more aminegroups, amides and triorganosilyl ethers.
 10. The composition of claim1, wherein the second styrene monomer is tert-butylstyrene.
 11. Thecomposition of claim 1, wherein the polystyrene copolymer furthercomprises styrene monomers substituted with one or more dye species.12-22. (canceled)
 23. A catalytic composition comprising a catalyticallyactive functional group bound to polyisobutylene.
 24. The composition ofclaim 23, wherein the catalytically active functional group comprises atriorganophosphine ligand.
 25. The composition of claim 23, wherein thecatalytically active functional group comprises an alkyldiarylphosphineligand.
 26. The composition of claim 23, wherein the catalyticallyactive functional group comprises a triorganophosphine ligand complexedwith palladium. 27-38. (canceled)